(59 days)
BioSieve™ Dx Marijuana Test Panel 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
BioSieve™ Dx Marijuana Test Strip 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
BioSieve™ Dx Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
BioSieve™ Dx Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
BioSieve™ Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
BioSieve™ Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
The BioSieve™ Marijuana Test Panel (Strip) and the BioSieve™ Dx Marijuana Test Panel (Strip) tests are immunochromatographic assays that use a lateral flow system for the qualitative detection of Marijuana in human urine. The products are single-use in vitro diagnostic devices. Each test kit contains a Test Device and a package insert. Each test device is sealed with a desiccant in an aluminum pouch.
The provided document describes the BioSieve™ Marijuana Test Panel and Test Strip devices for qualitative detection of Marijuana in human urine. Here's a breakdown of the acceptance criteria and study information:
1. Table of Acceptance Criteria and Reported Device Performance
The document doesn't explicitly state "acceptance criteria" for the overall device performance in a consolidated table, but rather presents performance characteristics of the device. From the precision study, it can be inferred that the device is expected to correctly identify drug-free samples and samples significantly above the cutoff, while showing a degree of variability around the cutoff. The provided precision data and the results of the comparison studies (with LC/MS) serve as the device's reported performance against implied accuracy and consistency expectations.
Inferred Acceptance Criteria / Performance Goals (based on Precision Study and Comparison Studies):
| Performance Characteristic | Acceptance Criteria (inferred) | Reported Device Performance (Summary) |
|---|---|---|
| Precision | Consistent results for samples well below and well above the cutoff. Some variability allowed around the cutoff concentrations (e.g., -25% to +25% of cutoff). Specifically, samples at -100%, -75%, -50% cut off should be negative, and samples at +50%, +75%, +100% cut off should be positive. Samples at -25% and +25% should show a mix of results, crossing the cutoff. This is implied by the study design and typical expectations for qualitative immunoassay cutoffs. | For 20 ng/mL Cut-off (Panel & Strip, across 3 lots):-100%, -75%, -50% cutoff: 100% negative.+50%, +75%, +100% cutoff: 100% positive.Results around cutoff (-25%, cutoff, +25%) show expected mixed results (e.g., at cutoff, 32-37 positive, 23-28 negative). |
| For 50 ng/mL Cut-off (Panel & Strip, across 3 lots):-100%, -75%, -50% cutoff: 100% negative.+50%, +75%, +100% cutoff: 100% positive.Results around cutoff (-25%, cutoff, +25%) show expected mixed results (e.g., at cutoff, 22-38 negative, 22-38 positive). | ||
| Accuracy (Comparison to LC/MS) | High agreement with LC/MS, especially for samples far from the cutoff. Close agreement for samples near the cutoff, while acknowledging some inherent variability in qualitative tests at the cutoff. | For 20 ng/mL Cut-off (Strip & Panel):High agreement for drug-free, low negative, and high positive samples. Mixed results for near-cutoff negative and positive samples, with some discordant results (false positives and false negatives relative to LC/MS at/near cutoff).For 50 ng/mL Cut-off (Strip & Panel):Similar high agreement for drug-free, low negative, and high positive samples, with expected mixed and discordant results around the cutoff. |
| Interference | No interference from common substances within specified concentrations. | No interference observed from 70+ substances at tested concentrations (e.g., 100µg/mL for most, 1% ethanol, 100 mg/dL albumin). |
| Specificity (Cross-Reactivity) | Predictable cross-reactivity with structurally similar compounds, with 100% cross-reactivity for the target analyte at the cutoff. Other cannabinoids show varying degrees of cross-reactivity (e.g., 1% for 11-Hydroxy-Δ9-Tetrahydrocannabinol). | Confirmed: 100% cross-reactivity for 11-nor-Δ9-THC-9-COOH and 11-Nor-Δ8-Tetrahydrocannabinol-9-COOH at respective cutoffs. Low cross-reactivity (0.5% - 1%) for Δ8-Tetrahydrocannabinol, Δ9-Tetrahydrocannabinol, and 11-Hydroxy-Δ9-Tetrahydrocannabinol. No cross-reactivity for Cannabinol and Cannabidiol at 100000 ng/mL. |
| Effect of Urine Specific Gravity & pH | No effect on accuracy within specified ranges. | No effect on accuracy/precision for specific gravity (1.000-1.035) and pH (4-9) at +/- 25% (or +/- 50%) cutoff levels. |
| Stability | Stable for a specified duration under defined storage conditions. | 24 months at 4-30°C based on accelerated and real-time stability studies. |
| Lay-user Comprehension | Instructions for use are easy to understand and follow, leading to correct test interpretation. | All participants found instructions easy to understand. Flesch-Kincaid read-ability score of Grade Level 7. Overall high percentage of correct results (95-100%) by lay users, with minor exceptions at -25% and +25% cutoff. |
2. Sample Size Used for the Test Set and Data Provenance
-
Precision Study Test Set:
- For each of the four device types (20 ng/mL Strip, 20 ng/mL Panel, 50 ng/mL Strip, 50 ng/mL Panel), 9 concentrations were tested (ranging from -100% cutoff to +100% cutoff).
- For each concentration, tests were performed two runs per day at each site for each of 3 lots for 10 days.
- This equates to: 9 concentrations * 2 runs/day * 3 sites * 3 lots * 10 days = 1620 tests per device type across all concentrations.
- Data Provenance: The document does not specify the country of origin for the samples or the study sites. It implies prospective testing as samples were "prepared by spiking 11-Nor-△9-THC-9-COOH in drug-free urine samples" and confirmed by LC/MS.
-
Comparison Studies Test Set (Algorithm Only/Standalone):
- For each of the four device types (20 ng/mL Strip, 20 ng/mL Panel, 50 ng/mL Strip, 50 ng/mL Panel), 80 unaltered urine samples were used.
- These 80 samples consisted of 40 negative and 40 positive samples, categorized further into: Drug-Free, Low Negative, Near Cutoff Negative, Near Cutoff Positive, and High Positive.
- Data Provenance: The document does not specify the country of origin of these "unaltered urine samples." It implies these are retrospective samples as they were blind-labeled and compared to LC/MS results.
-
Lay-user Study Test Set:
- 280 lay persons participated.
- Urine samples were prepared at 7 concentrations (-100%, -75%, -50%, -25%, +25%, +50%, +75% of 50 ng/mL cutoff).
- Each concentration used 20 samples.
- Each participant was given 1 blind-labeled sample. This means a total of 7 concentrations * 20 samples/concentration = 140 samples were tested across the 280 lay persons (since each person tested only one sample).
- Data Provenance: The document does not specify the country of origin. The samples were "prepared by spiking 11-Nor-△9-THC-9-COOH into drug free-pooled urine specimens," indicating prospective preparation.
3. Number of Experts Used to Establish the Ground Truth for the Test Set and Qualifications of Those Experts
- Precision and Comparison Studies: The ground truth for spiked samples (-100% cutoff to +100% cutoff for precision, and the various categories for comparison studies) was established by LC/MS (Liquid Chromatography-Mass Spectrometry). This is a highly accurate and widely accepted analytical method. The document does not mention human experts establishing this ground truth; the instrument itself provides the "truth."
- Lay-user Study: The ground truth for the lay-user study samples was also established by LC/MS confirming the drug concentrations after spiking.
4. Adjudication Method for the Test Set
- Precision Study: The results are presented as counts of positive/negative readings. No explicit adjudication method (like 2+1) is mentioned, as is common for analytical precision studies where each test's outcome is recorded.
- Comparison Studies: The individual operators' results (positive/negative) were directly compared to the LC/MS results. Discordant results are individually listed against the LC/MS result. There is no mention of an adjudication process among the operators.
- Lay-user Study: The lay users' obtained results (positive/negative) were compared against the LC/MS confirmed drug concentration of the sample they tested. No adjudication is mentioned.
5. If a Multi-Reader Multi-Case (MRMC) Comparative Effectiveness Study was done, If so, what was the effect size of how much human readers improve with AI vs without AI assistance
- No MRMC comparative effectiveness study was done, as this device is a standalone in-vitro diagnostic test kit (Strip/Panel), not an AI-assisted diagnostic tool for human readers. Therefore, there is no AI component, and no improvement effect size for human readers.
6. If a standalone (i.e. algorithm only without human-in-the-loop performance) was done
- Yes, standalone performance was evaluated by human observers interpreting the test results visually.
- The "Comparison Studies" section evaluates the device's performance by having six operators visually interpret the results of the strips/panels and compare them against LC/MS ground truth. This effectively determines the device's accuracy in a standalone setting (device + human interpretation) for laboratory professional users.
- The "Lay-user study" also evaluates the standalone performance by 280 lay persons visually interpreting the results.
7. The type of ground truth used
- The primary ground truth used for establishing drug concentrations and confirming results was LC/MS (Liquid Chromatography-Mass Spectrometry). This is considered a highly definitive analytical method for confirming drug presence and concentration.
8. The sample size for the training set
- The document does not mention a "training set" in the context of machine learning or AI. This is a traditional in-vitro diagnostic device (immunoassay) and therefore does not involve machine learning models that require training data. All samples described are used for performance validation and testing.
9. How the ground truth for the training set was established
- As there is no mention of a "training set" for a machine learning model, this question is not applicable to the described device. The samples used for performance evaluation (precision, comparison, lay-user studies) had their ground truth established by LC/MS confirmation of spiked drug concentrations or by direct LC/MS reference for unaltered urine samples.
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Image /page/0/Picture/0 description: The image contains the logo of the U.S. Food and Drug Administration (FDA). The logo consists of two parts: the Department of Health & Human Services logo on the left and the FDA logo on the right. The FDA logo features the letters 'FDA' in a blue square, followed by the words 'U.S. FOOD & DRUG ADMINISTRATION' in blue text.
VivaChek Biotech (Hangzhou) Co., Ltd % Joe Shia Director LSI International Inc 504 E Diamond Ave., Suite H Gaithersburg. Maryland 20877
Re: K231978
Trade/Device Name: BioSieve™ Marijuana Test Panel 50; BioSieve™ Marijuana Test Strip 50; BioSieve™ Dx Marijuana Test Strip 20; BioSieve™ Dx Marijuana Test Strip 50; BioSieve™ Dx Marijuana Test Panel 20; BioSieve™ Dx Marijuana Test Panel 50 Regulation Number: 21 CFR 862.3870 Regulation Name: Cannabinoid Test System Regulatory Class: Class II Product Code: NFW Dated: June 27, 2023 Received: July 3, 2023
Dear Joe Shia:
We have reviewed your Section 510(k) premarket notification of intent to market the device referenced above and have determined the device is substantially equivalent (for the indications for use stated in the enclosure) to legally marketed predicate devices marketed in interstate commerce prior to May 28, 1976, the enactment date of the Medical Device Amendments, or to devices that have been reclassified in accordance with the provisions of the Federal Food, Drug, and Cosmetic Act (Act) that do not require approval of a premarket approval application (PMA). You may, therefore, market the device, subject to the general controls provisions of the Act. Although this letter refers to your product as a device, please be aware that some cleared products may instead be combination products. The 510(k) Premarket Notification Database located at https://www.accessdata.fda.gov/scripts/cdrh/cfdocs/cfpmn/pmn.cfm identifies combination product submissions. The general controls provisions of the Act include requirements for annual registration, listing of devices, good manufacturing practice, labeling, and prohibitions against misbranding and adulteration. Please note: CDRH does not evaluate information related to contract liability warranties. We remind you, however, that device labeling must be truthful and not misleading.
If your device is classified (see above) into either class II (Special Controls) or class III (PMA), it may be subject to additional controls. Existing major regulations affecting your device can be found in the Code of Federal Regulations, Title 21, Parts 800 to 898. In addition, FDA may publish further announcements concerning your device in the Federal Register.
Please be advised that FDA's issuance of a substantial equivalence determination does not mean that FDA has made a determination that your device complies with other requirements of the Act or any Federal
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statutes and regulations administered by other Federal agencies. You must comply with all the Act's requirements, including, but not limited to: registration and listing (21 CFR Part 807); labeling (21 CFR Part 801 and Part 809); medical device reporting of medical device-related adverse events) (21 CFR 803) for devices or postmarketing safety reporting (21 CFR 4, Subpart B) for combination products (see https://www.fda.gov/combination-products/guidance-regulatory-information/postmarketing-safety-reportingcombination-products); good manufacturing practice requirements as set forth in the quality systems (QS) regulation (21 CFR Part 820) for devices or current good manufacturing practices (21 CFR 4, Subpart A) for combination products; and, if applicable, the electronic product radiation control provisions (Sections 531-542 of the Act); 21 CFR 1000-1050.
Also, please note the regulation entitled, "Misbranding by reference to premarket notification" (21 CFR Part 807.97). For questions regarding the reporting of adverse events under the MDR regulation (21 CFR Part 803), please go to https://www.fda.gov/medical-device-safety/medical-device-reportingmdr-how-report-medical-device-problems.
For comprehensive regulatory information about medical devices and radiation-emitting products, including information about labeling regulations, please see Device Advice (https://www.fda.gov/medicaldevices/device-advice-comprehensive-regulatory-assistance) and CDRH Learn (https://www.fda.gov/training-and-continuing-education/cdrh-learn). Additionally, you may contact the Division of Industry and Consumer Education (DICE) to ask a question about a specific regulatory topic. See the DICE website (https://www.fda.gov/medical-device-advice-comprehensive-regulatoryassistance/contact-us-division-industry-and-consumer-education-dice) for more information or contact DICE by email (DICE@fda.hhs.gov) or phone (1-800-638-2041 or 301-796-7100).
Sincerely,
Joseph A. Digitally signed by Kotarek -S Date: 2023.08.31
Kotarek -S 16:55:57 -04'00'
Joseph Kotarek Branch Chief Division of Chemistry and Toxicology Devices OHT7: Office of In Vitro Diagnostics Office of Product Evaluation and Quality Center for Devices and Radiological Health
Enclosure
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Indications for Use
510(k) Number (if known) K231978
Device Name
BioSieve™ Dx Marijuana Test Panel 20; BioSieve™ Dx Marijuana Test Panel 50 BioSieve™ Dx Marijuana Test Strip 20 BioSieve™ Dx Marijuana Test Strip 50
Indications for Use (Describe)
BioSieve™ Dx Marijuana Test Panel 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
BioSieve™ Dx Marijuana Test Strip 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
BioSieve™ Dx Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
BioSieve™ Dx Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
| Type of Use (Select one or both, as applicable) |
|---|
| Prescription Use (Rx - 21 CFR 801 Subpart D) |
| Over-The-Counter Use (21 CFR 801 Subpart C) |
| > Prescription Use (Part 21 CFR 801 Subpart D)
| | Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
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Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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Indications for Use
510(k) Number (if known) K231978
Device Name BioSieve™ Marijuana Test Panel 50 BioSieve™ Marijuana Test Strip 50
Indications for Use (Describe)
BioSieve™ Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
BioSieve™ Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL.
The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS or LC/MS is the preferred confirmatory method. For in vitro diagnostic use only.
| Type of Use (Select one or both, as applicable) |
|---|
| ------------------------------------------------- |
Prescription Use (Part 21 CFR 801 Subpart D)
X Over-The-Counter Use (21 CFR 801 Subpart C)
CONTINUE ON A SEPARATE PAGE IF NEEDED.
This section applies only to requirements of the Paperwork Reduction Act of 1995.
DO NOT SEND YOUR COMPLETED FORM TO THE PRA STAFF EMAIL ADDRESS BELOW.
The burden time for this collection of information is estimated to average 79 hours per response, including the time to review instructions, search existing data sources, gather and maintain the data needed and complete and review the collection of information. Send comments regarding this burden estimate or any other aspect of this information collection, including suggestions for reducing this burden, to:
Department of Health and Human Services Food and Drug Administration Office of Chief Information Officer Paperwork Reduction Act (PRA) Staff PRAStaff(@fda.hhs.gov
"An agency may not conduct or sponsor, and a person is not required to respond to, a collection of information unless it displays a currently valid OMB number."
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510(k) SUMMARY K231978
| 1 | Date | August 31, 2023 |
|---|---|---|
| 2 | Submitter | VivaChek Biotech (Hangzhou) Co., Ltd.Level 2, Block 2, 146 East Chaofeng Rd.Hangzhou, China |
| 3 | Contact Person | Joe ShiaLSI International Inc.504 East Diamond Ave., Suite JGaithersburg, MD 20877Telephone: 240-505-7880Fax: 301-916-6213Email: shiajl@yahoo.com |
| 4 | Device Name | BioSieve™ Dx Marijuana Test Panel 20BioSieve™ Dx Marijuana Test Panel 50 |
-
BioSieve™ Dx Marijuana Test Strip 20 BioSieve™ Dx Marijuana Test Strip 50 BioSieve™ Marijuana Test Panel 50 BioSieve™ Marijuana Test Strip 50
Class II -
5 Classification
| Product CodeTarget Drug | Regulation Section | Panel |
|---|---|---|
| NFWCannabinoids | 862.3870, Cannabinoids TestSystem | Toxicology |
-
- Predicate Device BIOEASY Marijuana Test Dip Card and BIOEASY Marijuana Test Strip (K192301)
-
- Intended Use
BioSieve™ Dx Marijuana Test Panel 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method.
For in vitro diagnostic use only.
BioSieve™ Dx Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method.
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For in vitro diagnostic use only.
BioSieve™ Dx Marijuana Test Strip 20 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 20 ng/mL The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method.
For in vitro diagnostic use only.
BioSieve™ Dx Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method.
For in vitro diagnostic use only.
BioSieve™ Marijuana Test Panel 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method.
For in vitro diagnostic use only.
BioSieve™ Marijuana Test Strip 50 is competitive binding, lateral flow immunochromatographic assay for qualitative detection of Marijuana in human urine at the cutoff concentrations of 50 ng/mL. The test provides only preliminary test results. A more specific alternative chemical method must be used in order to obtain a confirmed analytical result. GC/MS is the preferred confirmatory method.
For in vitro diagnostic use only.
-
- Device Description
The BioSieve™ Marijuana Test Panel (Strip) and the BioSieve™ Dx Marijuana Test Panel (Strip) tests are immunochromatographic assays that use a lateral flow system for the qualitative detection of Marijuana in human urine. The products are single-use in vitro diagnostic devices. Each test kit contains a Test Device and a package insert. Each test device is sealed with a desiccant in an aluminum pouch.
- Device Description
-
Proposed Device Item Predicate (K192301) For the qualitative determination of marijuana in human urine. Indication(s) for Same use
Substantial Equivalence Information 9.
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| Methodology | Competitive binding, lateral flow immunochromatographic assay based on antigen-antibody reaction | Same |
|---|---|---|
| Type of Test | Qualitative | Same |
| Specimen Type | Human urine | Same |
| Calibrator andCut-Off Values | 11-Nor-Δ9-THC-9-COOH20 ng/mL or 50 ng/mL | Same50 ng/mL |
| Configurations | Strip and Panel | Same |
| Intended Use | Prescription Use and over-the-counter use | Over-the-counter |
10. Test Principle
The BioSieve™ Marijuana Test Panel and the BioSieve™ Marijuana Test Strip tests are rapid tests for the qualitative detection of marijuana in urine samples. They are lateral flow chromatographic immunoassay. When urine sample is added to the device, urine is absorbed into the test strip and migrates upwards by capillary action. If the concentration of target drug presented in the urine sample is below the cutoff level, the target drug will not saturate the binding sites of its specific monoclonal antibody-coated particles. The antibody-coated particles will then be captured by immobilized drug-conjugate and a visible colored band will be formed on the test line region. If the concentration of target is beyond the cutoff level, the target drug will saturate the binding sites of its specific monoclonal antibody-particles, thus the antibody-coated particles will not be captured by immobilized drug-conjugate hence no colored band will be formed on the test line region.
A band should be formed on the control line region regardless of target drug or metabolite in the sample to indicate that the tests have been performed properly.
11. Performance Characteristics
-
- Analytical Performance
- a. Precision
Precision studies were carried out for samples with concentrations of -100% cut off, -75% cut off, -50% cut off, -25% cut off, cutoff, +25% cut off, +50% cut off, +75% cut off and +100% cut off at three different testing sites. Samples with concentration of -100% cutoff were drug-free urines samples. Other samples were prepared by spiking 11-Nor-△9-THC-9-COOH in drug-free urine samples. Each 11-Nor-△9-THC-9-COOH concentration was confirmed by LC/MS. For each concentration, tests were performed two runs per day at each site for each lot for 10 days. The results obtained are summarized in the following tables:
| drug | Result | ||||||||
|---|---|---|---|---|---|---|---|---|---|
| -100%cut off | -75%cut off | -50%cut off | -25%cut off | cut off | +25%cut off | +50%cut off | +75%cut off | +100%cut off | |
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 42-/18+ | 32+/28- | 46+/14- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 43-/17+ | 35+/25- | 42+/18- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 41-/19+ | 33+/27- | 45+/15- | 60+/0- | 60+/0- | 60+/0- |
For Strip Format of 20 ng/mL Cut-off:
For Panel Format 20 ng/mL Cut-off:
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| Result | -100% | -75% | -50% | -25% | cut off | +25% | +50% | +75% | +100% |
|---|---|---|---|---|---|---|---|---|---|
| drug | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off |
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 43-/17+ | 34+/26- | 44+/16- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 44-/16+ | 35+/25- | 46+/14- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 43-/17+ | 37+/23- | 45+/15- | 60+/0- | 60+/0- | 60+/0- |
| For Strip Format of 50 ng/mL Cut-off: | |||||||||
| Result | -100% | -75% | -50% | -25% | cut off | +25% | +50% | +75% | +100% |
| drug | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off |
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 24-/36+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 22-/38+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 23-/37+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| For Panel Format 50 ng/mL Cut-off: | |||||||||
| Result | -100% | -75% | -50% | -25% | cut off | +25% | +50% | +75% | +100% |
| drug | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off | cut off |
| Lot 1 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 30-/30+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 2 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 26-/34+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
| Lot 3 | 60-/0+ | 60-/0+ | 60-/0+ | 60-/0+ | 28-/32+ | 60+/0- | 60+/0- | 60+/0- | 60+/0- |
The following cutoff values are verified:
| Test Device | Cut-off values |
|---|---|
| BioSieve™ Marijuana Test Panel | 20 or 50 ng/mL |
| BioSieve™ Marijuana Test Strip | 20 or 50 ng/mL |
b. Linearity
Not applicable
c. Stability
The devices are stable at 4-30°C for 24 months based on accelerated and real time stability studies.
d. Interference
Potential interfering substances were added to drug-free urine samples with target drugs of -25% cutoff and +25% cutoff level and tested with 50ng/mL cut-off strip and panel devices. Potential interfering substances were added to drug-free urine samples with target drugs of -50% cutoff and +50% cutoff level and tested with 20ng/mL cut-off strip and panel devices. Compounds that show no interference at a concentration of 100µg/mL (albumin was tested at 100 mg/dL and ethanol was tested at 1%) are summarized in the following table.
| Acetaminophen | β-Estradiol | Oxalic acid |
|---|---|---|
| Acetophenetidin | Erythromycin | Oxolinic acid |
| N-Acetylprocainamide | Ethanol (1% v/v) | Oxymetazoline |
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| Acetylsalicylic acid | Fenoprofen | Papaverine |
|---|---|---|
| Albumin (100 mg/dL) | Furosemide | Penicillin G |
| Aminopyrine | Gentisic acid | Perphenazine |
| Amoxicillin | Hemoglobin | Phenelzine |
| Ampicillin | Hydralazine | Prednisone |
| Apomorphine | Hydrochlorothiazide | (±)-Propranolol |
| Ascorbic acid | Hydrocortisone | Pseudoephedrine |
| Aspartame | O-Hydroxyhippuric acid | Quinine |
| Atropine | 3-Hydroxytyramine | Ranitidine |
| Benzilic acid | Ibuprofen | Salicylic acid |
| Benzoic acid | Isoproterenol | Serotonin (5- Hydroxytyramine) |
| Bilirubin | Isoxsuprine | Sulfamethazine |
| Chloral hydrate | Ketamine | Sulindac |
| Chloramphenicol | Ketoprofen | Tetrahydrocortisone 3-(β-Dglucuronide) |
| Chlorothiazide | Labetalol | Tetrahydrocortisone 3-acetate |
| Chlorpromazine | Loperamide | Tetrahydrozoline |
| Cholesterol | Meperidine | Thiamine |
| Clonidine | Meprobamate | Thioridazine |
| Cortisone | Methoxyphenamine | Triamterene |
| (-)-Cotinine | Nalidixic acid | Trifluoperazine |
| Creatinine | Naloxone | Trimethoprim |
| Deoxycorticosterone | Naltrexone | DL-Tryptophan |
| Dextromethorphan | Naproxen | Tyramine |
| Diclofenac | Niacinamide | DL-Tyrosine |
| Diflunisal | Nifedipine | Uric acid |
| Digoxin | Norethindrone | Verapamil |
| Diphenhydramine | Noscapine | Zomepirac |
| Ecgonine methyl ester | (±)-Octopamine |
- Specificity e.
To test the specificity, drug metabolites and other components that are likely to cross-react in urine samples were spiked into drug-free urine. These urine samples were tested using three lots of each device.
Percent cross-reactivity, provided in the below table, was calculated as the cutoff concentration divided by the concentration of analyte tested that yielded a positive result, multiplied by 100; compounds that did not yield a positive result at the highest concentration tested have relative cross reactivity results represented by a dash in the table below:
| THC(Cannabinoids)(11-nor-Δ9-THC-9-COOH, Cut-off = 20 ng/mL) | Result | % Cross-Reactivity |
|---|---|---|
| 11-nor-Δ9-THC-9-COOH | 20 | 100% |
| 11-Hydroxy-Δ9-Tetrahydrocannabinol | 2000 | 1% |
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| 11-Nor-Δ8-Tetrahydrocannabinol-9-COOH | 20 | 100% |
|---|---|---|
| Cannabinol | 100000 | -- |
| Δ8-Tetrahydrocannabinol | 6000 | 0.5% |
| Δ9-Tetrahydrocannabinol | 6000 | 0.5% |
| Cannabidiol | 100000 | -- |
| 11-Nor-Δ9-THC-carboxy glucuronide | 40 | 50% |
| (-)-11-nor-9-carboxy-Δ9-THC | 20 | 100% |
| THC(Cannabinoids) | Result | % Cross-Reactivity |
|---|---|---|
| (11-nor-Δ9-THC-9-COOH, Cut-off = 50 ng/mL) | ||
| 11-nor-Δ9-THC-9-COOH | 50 | 100% |
| 11-Hydroxy-Δ9-Tetrahydrocannabinol | 5000 | 1% |
| 11-Nor-Δ8-Tetrahydrocannabinol-9-COOH | 50 | 100% |
| Cannabinol | 100000 | -- |
| Δ8-Tetrahydrocannabinol | 15000 | 0.5% |
| Δ9-Tetrahydrocannabinol | 15000 | 0.5% |
| Cannabidiol | 100000 | -- |
| 11-Nor-Δ9-THC-carboxy glucuronide | 100 | 50% |
| (-)-11-nor-9-carboxy-Δ9-THC | 50 | 100% |
f. Effect of Urine Specific Gravity and Urine pH
To investigate the effect of urine specific gravity, urine samples with specific gravity from 1.000 to 1.035 were spiked with target drugs at +25% cutoff and -25% cutoff levels for the 50 ng/mL cut-off devices. And the same urine specific gravity samples were spiked with target drugs at +50% cutoff and -50% cutoff levels for the 20 ng/mL cut-off devices. Three Operators tested each sample using test devices from three different lots. The results were all positive for samples at +25% cutoff or +50% cutoff and all negative for samples at -25% cutoff or -50% cutoff, indicating that urine specific gravity between 1.000 and 1.035 has no effect on the accuracy and precision of the test devices.
To investigate the effect of urine pH, urine samples with pH value from 4 to 9 were spiked with target drugs at +25% cutoff and -25% cutoff levels for the 50 ng/mL cut-off devices. And the same urine pH samples were spiked with target drugs at +50% cutoff and -50% cutoff levels for the 20 ng/mL cut-off devices. Three Operators tested each sample using test devices from three different lots. The results were all positive for samples at +25% or +50% cutoff and all negative for samples at -25% or -50% cutoff, indicating that urine pH value between 4.0 and 9.0 has no effect on the accuracy and precision of the test device.
2. Comparison Studies
The method comparison studies for BioSieve™ Marijuana Test Panel and BioSieve™ Marijuana Test Strip were performed with six operators. Operators ran 80 (40 negative and 40 positive) unaltered
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urine samples. The samples were blind labeled and compared to LC/MS results. The results are presented in the table below:
| For BioSieve™ Dx Marijuana Test Strip 20 | |||
|---|---|---|---|
| Drug-Free | LowNegative byLC-MS/MS(less than -50%) | Near CutoffNegative byLC-MS/MS(Between -50%and the Cutoff) | Near CutoffPositive by LC-MS/MS(Between thecutoff and+50%) | High Positiveby LC-MS/MS(greater than+50%) | ||
|---|---|---|---|---|---|---|
| Operator A | Positive | 0 | 0 | 1 | 17 | 22 |
| Negative | 10 | 16 | 13 | 1 | 0 | |
| Operator B | Positive | 0 | 0 | 2 | 16 | 22 |
| Negative | 10 | 16 | 12 | 2 | 0 | |
| Operator C | Positive | 0 | 0 | 2 | 16 | 22 |
| Negative | 10 | 16 | 12 | 2 | 0 |
Discordant Results:
| Operator | Sample Number | LC/MS Result (ng/mL) | BioSieve™ Result |
|---|---|---|---|
| Operator A | 22181 | 19.6 | + |
| Operator B | 22181 | 19.6 | + |
| Operator B | 22042 | 19.5 | + |
| Operator C | 22005 | 19.3 | + |
| Operator C | 22181 | 19.6 | + |
| Operator A | 22006 | 21.5 | - |
| Operator B | 22241 | 23.1 | - |
| Operator B | 22279 | 23.7 | - |
| Operator C | 22006 | 21.5 | - |
| Operator C | 22161 | 23.2 | - |
For BioSieve™ Dx Marijuana Test Panel 20
| Drug-Free | LowNegative byLC-MS/MS(less than -50%) | Near CutoffNegative byLC-MS/MS(Between -50%and the Cutoff) | Near CutoffPositive by LC-MS/MS(Between thecutoff and+50%) | High Positiveby LC-MS/MS(greater than+50%) | ||
|---|---|---|---|---|---|---|
| Operator A | Positive | 0 | 0 | 2 | 16 | 22 |
| Negative | 10 | 16 | 12 | 2 | 0 | |
| Operator B | Positive | 0 | 0 | 2 | 17 | 22 |
| Negative | 10 | 16 | 12 | 1 | 0 | |
| Operator C | Positive | 0 | 0 | 1 | 16 | 22 |
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| Negative | 10 | 16 | 13 | 2 | 0 | |
|---|---|---|---|---|---|---|
| -- | ---------- | ---- | ---- | ---- | --- | --- |
Discordant Results:
| Operator | Sample Number | LC/MS Result (ng/mL) | BioSieve™ Result |
|---|---|---|---|
| Operator D | 22071 | 19.3 | + |
| Operator D | 22073 | 19.6 | + |
| Operator E | 22071 | 19.3 | + |
| Operator E | 22204 | 19.5 | + |
| Operator F | 22073 | 19.6 | + |
| Operator D | 22205 | 23.7 | - |
| Operator D | 22302 | 21.5 | - |
| Operator E | 22302 | 21.5 | - |
| Operator F | 22016 | 23.2 | - |
| Operator F | 22302 | 21.5 | - |
For BioSieve™ Marijuana Test Strip 50
| Drug-Free | LowNegative byLC-MS/MS(less than -50%) | Near CutoffNegative byLC-MS/MS(Between -50%and the Cutoff) | Near CutoffPositive by LC-MS/MS(Between thecutoff and+50%) | High Positiveby LC-MS/MS(greater than+50%) | ||
|---|---|---|---|---|---|---|
| Operator A | Positive | 0 | 0 | 2 | 16 | 22 |
| Negative | 10 | 16 | 12 | 2 | 0 | |
| Operator B | Positive | 0 | 0 | 2 | 16 | 22 |
| Negative | 10 | 16 | 12 | 2 | 0 | |
| Operator C | Positive | 0 | 0 | 1 | 16 | 22 |
| Negative | 10 | 16 | 13 | 2 | 0 |
Discordant Results:
| Operator | Sample Number | LC/MS Result (ng/mL) | BioSieve™ Result |
|---|---|---|---|
| Operator A | 22172 | 49.2 | + |
| Operator A | 22318 | 46.8 | + |
| Operator B | 22115 | 47.8 | + |
| Operator B | 22172 | 49.2 | + |
| Operator C | 22172 | 49.2 | + |
| Operator A | 22013 | 50.5 | - |
| Operator A | 22237 | 50.9 | - |
| Operator B | 22237 | 50.9 | - |
| Operator B | 22284 | 53.9 | - |
| Operator C | 22013 | 50.5 | - |
| Operator C | 22237 | 50.9 | - |
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| Drug-Free | LowNegative byLC-MS/MS(less than -50%) | Near CutoffNegative byLC-MS/MS(Between -50%and the Cutoff) | Near CutoffPositive by LC-MS/MS(Between thecutoff and+50%) | High Positiveby LC-MS/MS(greater than+50%) | ||
|---|---|---|---|---|---|---|
| Operator A | Positive | 0 | 0 | 1 | 16 | 22 |
| Negative | 10 | 16 | 13 | 2 | 0 | |
| Operator B | Positive | 0 | 0 | 1 | 16 | 22 |
| Negative | 10 | 16 | 13 | 2 | 0 | |
| Operator C | Positive | 0 | 0 | 2 | 16 | 22 |
| Negative | 10 | 16 | 12 | 2 | 0 |
Discordant Results:
| Operator | Sample Number | LC/MS Result (ng/mL) | BioSieve™ Result |
|---|---|---|---|
| Operator D | 22217 | 46.8 | + |
| Operator E | 22206 | 49.2 | + |
| Operator F | 22017 | 47.8 | + |
| Operator F | 22206 | 49.2 | + |
| Operator D | 22137 | 50.9 | - |
| Operator D | 22152 | 53.9 | - |
| Operator E | 22103 | 50.5 | - |
| Operator E | 22137 | 50.9 | - |
| Operator F | 22103 | 50.5 | - |
| Operator F | 22152 | 53.9 | - |
Lay-user study:
A lay user study was performed at three intended user sites with 280 lay persons for the devices. The lay users had diverse educational and professional backgrounds and ranged in age from 18 to > 50 years. Urine samples were prepared at the following concentrations; negative, +/- 75%, +/-50%, +/-25% of the 50 ng/mL cutoff by spiking 11-Nor-△9-THC-9-COOH into drug free-pooled urine specimens. The concentrations of the samples were confirmed by LC/MS. Each sample was aliquoted into individual containers and blind-labeled. Each participant was provided with the package insert, 1 blind labeled sample and a device. Each device was tested. Summary results are shown below.
The results summary for strip format:
| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results (%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative |
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| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
|---|---|---|---|---|---|
| -75% Cutoff | 20 | 12 | 0 | 20 | 100 |
| -50% Cutoff | 20 | 24.5 | 0 | 20 | 100 |
| -25% Cutoff | 20 | 36.2 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 60.9 | 20 | 0 | 100 |
| +50% Cutoff | 20 | 76.2 | 20 | 0 | 100 |
| +75% Cutoff | 20 | 90.5 | 20 | 0 | 100 |
The results summary for panel format:
| % of Cutoff | Number ofsamples | Drug ConcentrationbyLC/MS/MS(ng/mL) | Lay person Results | The percentage ofcorrect results (%) | |
|---|---|---|---|---|---|
| No. ofPositive | No. ofNegative | ||||
| -100% Cutoff | 20 | 0 | 0 | 20 | 100 |
| -75% Cutoff | 20 | 12 | 0 | 20 | 100 |
| -50% Cutoff | 20 | 24.5 | 0 | 20 | 100 |
| -25% Cutoff | 20 | 36.2 | 1 | 19 | 95 |
| +25% Cutoff | 20 | 60.9 | 19 | 1 | 95 |
| +50% Cutoff | 20 | 76.2 | 20 | 0 | 100 |
| +75% Cutoff | 20 | 90.5 | 20 | 0 | 100 |
Participants were given surveys on the ease of understanding the instruction for use. All participants indicated that the device instruction is easy to understand and follow. A Flesch-Kincaid reading analysis was performed on each package insert and the scores revealed a reading Grade Level of 7.
Clinical Studies:
Not applicable.
12. Conclusion
Based on the test principle and performance characteristics of the device including precision, cut-off, interference, specificity, method comparison and lay-user studies of the devices, it's concluded that BioSieve™ Marijuana Test Panel and BioSieve™ Marijuana Test Strip are substantially equivalent to the predicate device.
§ 862.3870 Cannabinoid test system.
(a)
Identification. A cannabinoid test system is a device intended to measure any of the cannabinoids, hallucinogenic compounds endogenous to marihuana, in serum, plasma, saliva, and urine. Cannabinoid compounds includedelta -9-tetrahydrocannabinol, cannabidiol, cannabinol, and cannabichromene. Measurements obtained by this device are used in the diagnosis and treatment of cannabinoid use or abuse and in monitoring levels of cannabinoids during clinical investigational use.(b)
Classification. Class II (special controls). A cannabinoid test system is not exempt if it is intended for any use other than employment or insurance testing or is intended for Federal drug testing programs. The device is exempt from the premarket notification procedures in subpart E of part 807 of this chapter subject to the limitations in § 862.9, provided the test system is intended for employment and insurance testing and includes a statement in the labeling that the device is intended solely for use in employment and insurance testing, and does not include devices intended for Federal drug testing programs (e.g., programs run by the Substance Abuse and Mental Health Services Administration (SAMHSA), the Department of Transportation (DOT), and the U.S. military).